The development and design of the European Board of Otorhinolaryngology-Head and Neck Surgery Examination (EBEORL-HNS).

The UEMS Otorhinolaryngology-Head and Neck Surgery section is a dedicated body formed to promote the standardisation and harmonisation of European Otorhinolaryngology (ORL). The European Examination Board of Otorhinolaryngology and Head and Neck Surgery was created to establish a supranational final exam and accreditation for ORL Surgeons. It is open to candidates both from the European Union and outside the EU. The exam is composed of a written examination to assess mainly the theoretical knowledge of Otorhinolaryngological diseases. The second part, a viva voce examination, is designed to test the clinical application of knowledge based on case scenarios and clinical conditions presented to the candidates. The inaugural examination written component took place in Mannheim/Germany in 2009 and the inaugural Viva Voce examination in Vienna/Austria in 2010. Up to and including the year 2013, 858 participants have attempted one of the two exam components. Of the 858 participants, 305 were successful in both examinations and obtained the accreditation of the European Diploma (European Board Certification). The historical origins, development of the examination, its formal arrangements and the format of the examination are presented in this article.

Fusion of the 2nd with the 3rd Cervical Vertebrae (C2-C3): A Case Series with Possible Clinical Significance.

Purpose: The current case series describes three cases of fusion between the 2nd cervical vertebra, the axis (C2), and the 3rd cervical vertebra (C3), creating a C2-C3 osseous complex and highlighting its morphological type of fusion (partial or complete) and morphometric details. The developmental background of this complex is emphasized, pointing out the possible clinical significance. Materials and Methods: The osseous complexes were derived from disarticulated skeletons of body donors and were collected from the osseous collection of the Anatomy Department of the Medical School of the National and Kapodistrian University of Athens. Results: Three blocked vertebral complexes (2 partial and 1 complete C2-C3 osseous masses) were identified. In two cases, the vertebral bodies were partially fused and in one case were completely fused. In the 1st case, the C2-C3 complex had fused spinous processes and distinct transverse processes. Facets were completely fused on the left and partially fused on the right side. In the 2nd case, the C2-C3 complex had partially fused vertebral bodies and distinguishable spinous processes. In the 3rd case, the C2-C3 complex had completely fused vertebral bodies, facets, laminae, and transverse and spinous processes. Conclusions: Among the three (C2-C3) fused osseous complexes, the two were partially and the one was completely ossified. The fused vertebrae were characterized by osteophytic formations (at the dens and C3 area) and osteoporotic lesions. Taking into consideration the C2-C3 fusion, and possible coexisted variants, particular caution should be made in the upper cervical area, to interpret possible neurological manifestations and to reach a safe surgical plan.

Quality of Life After Total Laryngectomy: A Retrospective Study.

Quality of life is severely affected in laryngeal cancer patients, who have undergone total laryngectomy, particularly with regard to cancer diagnosis and the consequences of total laryngectomy. The aim of the present study is to record and evaluate the problems related with the quality of life in laryngectomized patients. A further goal is to investigate, whether a correlation exists between demographics and clinical characteristics of the patients. Fifty male patients, who underwent total laryngectomy, participated in the study. Two questionnaires were used to test various quality of life parameters, the EORTC QLQ C30 version 3.0 and EORTC QLQ H&N35. Specific demographic and clinical data of the patients were also recorded. The overall quality of life index was similar in both studied patients and the reference group of cancer patients provided by the European Organization for Research and Treatment of Cancer (EORTC). However, the following discrepancies were noted: voice, senses, dyspnoea were more problematic in studied patients, whereas the functional status of cognitive, physical, social and emotional function were better. In most recorded symptoms, the intensity was mild. The demographic and clinical data appeared to have interesting correlations with specific functional aspects and symptoms. Although several quality of life aspects are found to be negatively affected in laryngectomized patients, overall quality of life appears to be satisfactory.

Genetic Variation in the Vascular Endothelial Growth Factor (VEGFA) Gene at rs13207351 Is Associated with Overall Survival of Patients with Head and Neck Cancer.

Head and neck cancer (HNC) is a significantly heterogeneous disease and includes malignancies arising from different anatomical sites, such as nasopharyngeal cancer (NPC) and laryngeal cancer (LC). In the current study, polymorphisms located in angiogenesis- and apoptosis-related genes (VEGFA, FAS, EDNRA and NBS1) were evaluated regarding their clinical significance in HNC patients. In total, 333 HNC patients were enrolled in this study and 34 variants located on the aforementioned genes were genotyped via Sanger sequencing. LC patients, homozygous A for VEGFA rs13207351, had shorter overall survival (OS) as opposed to homozygous G (Hazard ratio (HR) = 2.06, Wald's p = 0.017) upon adjustment for age, disease stage, and surgery. Following the dominant model, LC patients carrying the A allele had a marginally significantly higher risk for death (HR = 1.72, p = 0.059). NPC patients heterozygous (CT) for FAS rs2234768 had a marginal but significantly higher risk of death compared to those with homozygosity for the T allele (HR = 2.22, p = 0.056). In conclusion, rs13207351 (VEGFA) and rs2234768 (FAS) polymorphisms seem to have prognostic significance in HNC, with VEGFA rs13207351 showing the most promise in this subgroup of LC patients.

Tumor Infiltrating Lymphocytes and CD8+ T Cell Subsets as Prognostic Markers in Patients with Surgically Treated Laryngeal Squamous Cell Carcinoma.

To evaluate the prognostic significance of tumor infiltrating lymphocytes (TILs) and of CD8+ T-cell subsets in patients with surgically treated laryngeal squamous cell carcinoma (LSCC), LSCC from 283 patients were examined. TIL density was morphologically assessed on whole sections. CD8+ cell counts/mm2 were evaluated on multiple tissue microarray cores per tumor (median counts for high/low CD8+/mm2). TIL density and CD8+ counts weakly correlated with each other (Spearman's rho = 0.348). Heterogeneous CD8+ counts/mm2 were demonstrated in 28% of the tumors. In univariate analysis, a significant interaction was observed between CD8 expression and nodal status with respect to outcome; in node-positive patients, those with high CD8+ tumors had 77% lower risk of relapse (interaction p < 0.001) and 74% lower risk for death (interaction p = 0.002) compared to patients with low CD8+ tumors. In multivariate analysis, higher TIL density independently conferred lower risk for relapse in the entire cohort (HR 0.87; 95% CI 0.77-0.98; Wald's p = 0.017) and in node-positive patients (HR 0.41; 95% CI 0.23-0.75; p = 0.003) and, similarly, for death (p = 0.025 and p = 0.003, respectively). High CD8+ was not a significant independent prognostic marker in any analysis setting. The assessment of CD8+ infiltrates does not seem to offer additional prognostic information over the morphologically assessed TIL density. It also appears that the favorable prognostic impact of higher TIL density and CD8+ infiltrates mostly concerns node-positive but not node-negative disease. If validated in larger node-positive cohorts, these findings are worth considering for the diagnostic development of immune cell infiltrates in LSCC.

Morganella Morganii: An Unusual Case-Report of Shoulder Septic Arthritis.

Morganella morganii is a gram-negative, anaerobic, facultative bacillus that is part of the natural flora of the gastrointestinal system. In the rare event of joint effusion, it is known for its slow-paced progression of symptoms and occasional attacks and remissions leading to septic arthritis, and it is difficult to recognize and to address with a timely response. We present a case of a 95-year-old male hospitalized due to left shoulder septic arthritis. The symptoms commenced as simple discomfort in the joint, and 10 days later this was followed with pain and dysfunction, diffusion, and mild fever. Blood and pus cultures were obtained on the day of admission; arthroscopic debridement was performed the next morning; and wide-spectrum antibiotic treatment was initiated. Both blood and pus cultures isolated Morganella morganii, and the antibiotic regimen was adjusted to the antibiogram. Clinical and laboratory scores demonstrated signs of improvement, and the patient recovered within 3 months.

Endoscopic Retrograde Cholangiopancreatography for Ampullary Carcinomas: Friend or Foe?

The role of preoperative endoscopic retrograde cholangiopancreatography (ERCP) in ampullary carcinomas is under debate due to potential associated complications. We report the case of a 59-year-old male diagnosed with ampullary cancer, who had undergone ERCP that was followed by bleeding and perforation. We conclude that interventions before surgical resection, including ERCP, may compromise patient outcome.

Endoscopic Resection of Sinonasal Inverted Papilloma: Systematic Review and Meta-Analysis.

Background Pure endoscopic surgery (functional endoscopic sinus surgery) has been increasingly replacing external approaches in the management of sinonasal inverted papillomas. Objective To analyze and compare the effectiveness of pure endoscopic procedure with external or combined procedures to paranasal inverted papillomas, including the experience from two institutions in North Greece, over a 20-year period. Methods Systematic literature searches of MEDLINE (1952-2016), EMBASE (1974-2016), and the Cochrane Central Register of Controlled Trials. Review of all English-language studies comparing endoscopic and open techniques. Odds ratios (ORs), risk ratio, 95% confidence intervals (CIs), and tests for heterogeneity were reported. Recurrence rates according to initial tumor stage. Results In total, 2451 patients had been enrolled in the 23 studies, published between 1992 and 2014. All the included articles are graded as level IV evidence. Among the 1526 patients of the endoscopic group, 212 (13.8%) had recurrence, with the mean time of recurrence to range from 14 to 46.6 months. In the external approach group, 111 (18.7%) of the 592 patients had recurrence, with the time of recurrence to range from 7 to 92 months. The recurrence rate in the combined approach group was 12.9%. The occurrence rate of recurrence attributable to the surgical choice was significantly different between endoscopic and external group (OR: 0.61; 95% CI: 0.40-0.92; P = 0.02; 14.9% vs. 18.8% in endoscopic and external group, respectively). Conclusions The present systematic review and meta-analysis indicates that endoscopic approach seems a favorable treatment option of sinonasal inverted papillomas and confirms the global recommendation that is the gold standard in the treatment of such nose lesions, revealing a lower recurrence rate compared to external approaches.

Paclitaxel, cisplatin, leucovorin, and continuous infusion fluorouracil followed by concomitant chemoradiotherapy for locally advanced squamous cell carcinoma of the head and neck: a Hellenic Cooperative Oncology Group Phase II Study.

The primary objective of this phase II study was to access the complete response (CR) rate to a new innovative induction regimen in patients with locally advanced head and neck cancer (LA-HNC). From October 2000 until October 2003 a total of 38 eligible patients (33 men and 5 women) entered the study. The large majority of them presented with a performance status of 0-1 and with clinical stage IV disease. Treatment consisted of three cycles of induction chemotherapy (IC) with paclitaxel 175 mg/m2 in a 3-h infusion on d 1, leucovorin (LV) 200 mg/m2 over 20 min immediately followed by FU 400 mg/m2 bolus and then 600 mg/m2 as a 24-h continuous infusion on d 1 and 2 and a cisplatin 75 mg/m2 over 1-h infusion on d 2 every 3 wk. This was then followed by radiation (70 Gy) and weekly cisplatin 40 mg/m2. After the completion of IC, 6/38 (16%) patients had CR. The CR rate was increased to 66% post-concomitant chemoradiotherapy (CCRT). Neutropenia (37.5%), pain (62%), nausea/vomiting (21%), and alopecia (79%) were the most frequent side effects during IC. The most pronounced toxicities during chemoradiotherapy were stomatitis (62.5%) and xerostomia (53%). Median time to progression was 11.0 mo and median survival 16.7 mo. One- and 2-yr survival rates were 73% and 38%, respectively. In conclusion, this novel induction regimen is active, is well tolerated, and can be successfully followed by CCRT with weekly cisplatin. CCRT should remain standard treatment for patients with LA-HNC. Novel induction combinations, such as that reported in the present study, should be evaluated in combination with CCRT only in the context of clinical trials.

An extremely rare case of synchronous occurrence in the larynx of intravascular lymphoma and in situ squamous cell carcinoma.

We present the first case of laryngeal intravascular lymphoma coexisting with in situ squamous cell carcinoma. The patient, a 53 years old man, presented with hoarseness starting a year ago and underwent laryngoscopy, which revealed two nodular lesions on his right vocal cord. The histological and immunohistochemical examination of the biopsy specimens established the diagnosis of in situ squamous cell carcinoma coexisting with intravascular lymphoma of T-cell origin. Taking in consideration all the available references, the larynx has not until now been reported as a primary site of involvement of intravascular (angiotropic) lymphomas, nor as a secondary location in the systematic course of this disease. Furthermore no cases have been reported in the literature, concerning the synchronous affection of the larynx by this lymphoma and in situ laryngeal carcinoma, or other type of neoplasm.

Concomitant radiochemotherapy vs radiotherapy alone in patients with head and neck cancer: a Hellenic Cooperative Oncology Group Phase III Study.

The primary objective of the present randomized phase III trial was to compare the 3-yr survival rate of patients treated with standard fractionated radiotherapy (RT) alone or with the same RT concomitantly with cisplatin (DDP) or carboplatin (Cb). From January 1995 until July 1999, 124 patients with histologically proven locally advanced non-nasopharyngeal head and neck cancer (HNC) were randomized to receive either RT monotherapy (70 Gy, Group A) or the same RT concomitantly with DDP (100 mg/m2 on d 2, 22, 42, Group B) or Cb (7 AUC on d 2, 22, 42, Group C). There were no significant differences in complete response rates between patients treated with RT alone or combined chemoradiotherapy. However, median time to progression (TTP) and overall survival (OS) were significantly longer in patients treated with concomitant chemoradiotherapy. Thus, median TTP was 6.3, 45.2, and 17.7 mo in groups A, B, and C respectively (p = 0.0002). Similarly, median OS was 12.2, 48.6, and 24.5 mo, respectively (p = 0.0003). At 3 yr follow-up, 17.5% of patients in group A were alive compared to 52% in group B and 42% in group C (p < 0.001). Patients treated with concomitant chemoradiotherapy experienced more frequently severe hematological toxicity. Also, severe nausea/vomiting was more pronounced in group B, as expected. The present study clearly demonstrated that concomitant chemoradiotherapy with platinum analogs significantly prolongs 3-yr survival and median OS in patients with locally advanced HNC compared to conventional RT alone.

Evaluation of various therapeutic schemes in the treatment of tinnitus due to acute acoustic trauma.

OBJECTIVES: We evaluated the effectiveness of various pharmaceutical therapeutic schemes in the treatment of tinnitus due to acute acoustic trauma. PATIENTS AND METHODS: This prospective study included 108 military personnel (all males; mean age 22 years; range 18 to 31 years) with complaints of tinnitus due to acute acoustic trauma following firearm use. Involvement was in the left ear in 61 patients, the right ear in nine patients, and in both ears in 38 patients. The mean duration from trauma to treatment was 26 days (range 1 to 110 days). Before and after treatment, complaints of tinnitus were evaluated using a questionnaire and a visual analog scale. Treatment was carried out for 15 days in four randomized groups: oral administration of trimetazidine, prednisolone, and vitamin B complex; trimetazidine alone; prednisolone and vitamin B complex; and intravenous piracetam and prednisolone. Unresponsive patients were further treated with trimetazidine for a month. Evaluations were made 15 days and 45 days after the institution of treatment. RESULTS: Thirteen patients (12%) had complete remission and 28 patients (25.9%) showed significant improvement. Further treatment with trimetazidine was beneficial in only seven (9.5%) patients. No significant differences were found between the groups in terms of tinnitus remission and improvement in hearing (p>0.05). Initiation of treatment, especially within the first week following acoustic trauma was significantly linked with higher rates of tinnitus regression (p<0.05). The degree of hearing improvement after medication did not correlate with improvement in tinnitus. Intravenous treatment was not advantageous over oral treatment. CONCLUSION: A timely initiation of therapy, especially within the first week following acoustic trauma, increases the chance of improvement in tinnitus patients.

Protein and mRNA expression of notch pathway components in operable tumors of patients with laryngeal cancer.

BACKGROUND: There exist substantial evidence that laryngeal cancer represents a unique entity among squamous head and neck carcinomas. MATERIALS AND METHODS: Tumors from 289 patients with squamous cell laryngeal cancer were assessed for protein (immunohistochemistry) and mRNA (qRT-PCR) expression of Notch pathway components (Notch1 to 4 receptors and Jagged1 ligand) on tissue microarrays. RESULTS: In univariate analysis, enhanced nuclear Jagged1 expression conferred a longer disease-free survival (DFS) (p=0.013) and overall survival (OS) (p=0.004), in contrast to the unfavorable prognostic value of Notch3 for both DFS (p=0.009) and OS (p=0.024). In multivariate analysis, overexpression of either Notch or cytoplasmic Jagged1 conferred an unfavorable effect on DFS (Hazard Ratio=1.88, 95% Confidence Interval=1.03-3.43, p=0.04). CONCLUSION: Our study indicates a consistent unfavorable effect of Notch3 and cytoplasmic Jagged1 protein expression, a favorable impact of nuclear Jagged 1 localization, and a differential prognostic value of Notch2 expression according to the presence of cytoplasmic Jagged 1.

Prognostic significance of the Wnt pathway in squamous cell laryngeal cancer.

OBJECTIVES: We sought to determine the prognostic significance of the Wnt signaling pathway in operable squamous cell carcinoma of the larynx. MATERIALS AND METHODS: In an annotated cohort of 289 operable laryngeal cancers we evaluated the prognostic impact of E-cadherin, P-cadherin and ß-catenin protein expression with immunohistochemistry, as well as the mRNA expression of 7 key effectors of the Wnt pathway including secreted frizzled-related protein 4 (SFRP4), SNAI2 (SLUG) and WNT5A with qPCR (relative quantification [RQ]). RESULTS: Using median immunoreactive scores as a pre-defined cut-off, patients whose tumors overexpressed both cytoplasmic E-cadherin and ß-catenin experienced longer median OS as compared to those whose tumors overexpressed ß-catenin only (median OS 124 vs. 72 months, p=0.0301) and patients whose tumors overexpressed both cytoplasmic and membranous E-cadherin experienced longer DFS as compared to those whose tumors overexpressed cytoplasmic E-cadherin only (median 118 vs. 91 months, p=0.0106). Upon hierarchical clustering of SFRP4, SNAI2 and WNT5A RQ values, profiles including co-expression of all 3 genes but also profiles with under-expression of SNAI2 and WNT5A were associated with worse outcome as compared to profiles not related to the Wnt pathway. In multivariate analysis, clustering was an independent predictor for DFS (p=0.0221) and OS (p=0.0077). CONCLUSION: We identified gene expression profiles and IHC patterns associated with aberrant Wnt signaling conferring aggressive clinical behavior in operable squamous cell carcinoma of the larynx. Prospective validation of these results will determine whether targeting the Wnt pathway merits investigation in this disease.

Primary neuroendocrine neoplasms of the larynx. A series of 4 cases reported and a review of the literature.

BACKGROUND: Neuroendocrine tumors are rare neoplasms arising from neural and epithelial origin. METHODS AND RESULTS: The case records of 4 patients with the diagnosis of neuroendocrine laryngeal tumor were retrospectively reviewed. In this analysis of our medical records, we describe a series of 4 men with neuroendocrine laryngeal tumors treated in our department since 1994, including the first extremely aggressive and lethal laryngeal paraganglioma reported in the English-language literature. We also discuss the classification, the macro and microscopical characteristics, clinical and pathologic findings, and treatment of these neoplasms. CONCLUSION: Although neuroendocrine laryngeal tumors account for approximately 1% of all neoplasms in the larynx, its majority represents very aggressive tumors showing a capacity for metastasis and portending poor outcome.

Insulin-like growth factor 1 receptor (IGF1R) expression and survival in operable squamous-cell laryngeal cancer.

INTRODUCTION: Prognosis of patients with operable laryngeal cancer is highly variable and therefore potent prognostic biomarkers are warranted. The insulin-like growth factor receptor (IGFR) signaling pathway plays a critical role in laryngeal carcinogenesis and progression. PATIENTS AND METHODS: We identified all patients with localized TNM stage I-III laryngeal cancer managed with potentially curative surgery between 1985 and 2008. Immunohistochemical (IHC) expression of IGF1R-alpha, IGF1R-beta and IGF2R was evaluated using the immunoreactive score (IRS) and mRNA levels of important effectors of the IGFR pathway were assessed, including IGF1R, IGF-binding protein 3 (IGFBP3), suppressor of cytokine signaling 2 (SOCS2) and members of the MAP-kinase (MAP2K1, MAPK9) and phosphatidyl-inositol-3 kinase (PIK3CA, PIK3R1) families. Cox-regression models were applied to assess the predictive value of biomarkers on disease-free survival (DFS) and overall survival (OS). RESULTS: Among 289 eligible patients, 95.2% were current or ex smokers, 75.4% were alcohol abusers, 15.6% had node-positive disease and 32.2% had received post-operative irradiation. After a median follow-up of 74.5 months, median DFS was 94.5 months and median OS was 106.3 months. Using the median IRS as the pre-defined cut-off, patients whose tumors had increased IGF1R-alpha cytoplasm or membrane expression experienced marginally shorter DFS and significantly shorter OS compared to those whose tumors had low IGF1R-alpha expression (91.1 vs 106.2 months, p = 0.0538 and 100.3 vs 118.6 months, p = 0.0157, respectively). Increased mRNA levels of MAPK9 were associated with prolonged DFS (p = 0.0655) and OS (p = 0.0344). In multivariate analysis, IGF1R-alpha overexpression was associated with a 46.6% increase in the probability for relapse (p = 0.0374). Independent predictors for poor OS included node-positive disease (HR = 2.569, p<0.0001), subglottic/transglottic localization (HR = 1.756, p = 0.0438) and IGF1R-alpha protein overexpression (HR = 1.475, p = 0.0504). CONCLUSION: IGF1R-alpha protein overexpression may serve as an independent predictor of relapse and survival in operable laryngeal cancer. Prospective evaluation of the IGF1R-alpha prognostic utility is warranted.

Identification and validation of a multigene predictor of recurrence in primary laryngeal cancer.

PURPOSE: Local recurrence is the major manifestation of treatment failure in patients with operable laryngeal carcinoma. Established clinicopathological factors cannot sufficiently predict patients that are likely to recur after treatment. Additional tools are therefore required to accurately identify patients at high risk for recurrence. This study attempts to identify and independently validate gene expression models, prognostic of disease-free survival (DFS) in operable laryngeal cancer. MATERIALS AND METHODS: Using Affymetrix U133A Genechips, we profiled fresh-frozen tumor tissues from 66 patients with laryngeal cancer treated locally with surgery. We applied Cox regression proportional hazards modeling to identify multigene predictors of recurrence. Gene models were then validated in two independent cohorts of 54 and 187 patients (fresh-frozen and formalin-fixed tissue validation sets, respectively). RESULTS: We focused on genes univariately associated with DFS (p<0.01) in the training set. Among several models comprising different numbers of genes, a 30-probe set model demonstrated optimal performance in both the training (log-rank, p<0.001) and 1(st) validation (p=0.010) sets. Specifically, in the 1(st) validation set, median DFS as predicted by the 30-probe set model, was 34 and 80 months for high- and low-risk patients, respectively. Hazard ratio (HR) for recurrence in the high-risk group was 3.87 (95% CI 1.28-11.73, Wald's p=0.017). Testing the expression of selected genes from the above model in the 2(nd) validation set, with qPCR, revealed significant associations of single markers, such as ACE2, FLOT1 and PRKD1, with patient DFS. High PRKD1 remained an unfavorable prognostic marker upon multivariate analysis (HR=2.00, 95% CI 1.28-3.14, p=0.002) along with positive nodal status. CONCLUSIONS: We have established and validated gene models that can successfully stratify patients with laryngeal cancer, based on their risk for recurrence. It seems worthy to prospectively validate PRKD1 expression as a laryngeal cancer prognostic marker, for routine clinical applications.

Dermatofibrosarcoma protuberans with fibrosarcomatous transformation of the head and neck.

Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous neoplasm associated with a high cure rate. We present a case of aggressive DFSP with fibrosarcomatous areas in the head and neck. A 28-year-old Mediterranean female presented with a 45-day history of rapidly growing cutaneous lesion of the face. Surgical biopsy confirmed the diagnosis of DFSP. Subsequently, the patient underwent wide local surgical resection, followed by reconstruction. Histopathology report revealed fibrosarcomatous transformation and the patient underwent adjuvant radiotherapy. The patient continues to be disease free at the 35-month follow-up.Although DFSP behave as non-aggressive malignancy, surgery with complete removal of the affected area is the intervention of choice. Moreover, adjuvant treatment and follow-up of the patient is essential in order to prevent recurrence.

STAT-Related Profiles Are Associated with Patient Response to Targeted Treatments in Locally Advanced SCCHN.

The anti-epidermal growth factor receptor antibody cetuximab (Erbitux, CTX) is currently used for the treatment of locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN), as yet with modest effectiveness, prompting for the identification of response predictors to this treatment and for the targeting of additional pathways implicated in this disease. Within this scope, we investigated the effect of SRC/STAT pathway components on LA-SCCHN patient outcome. SRC, STAT1, STAT3, STAT5A, STAT5B, ANXA1, CAV1, IGFBP2, EPHA2, EPHB2, and MSN relative gene expression, as well as Stat protein activation, were assessed on LA-SCCHN tumor tissues from 35 patients treated with combined radiotherapy (RT) and CTX-based regimens. Stat1, Stat3, and Stat5 proteins were usually found activated in neoplastic nuclei (70.4%, 85.7%, and 70.8%, respectively). Activated Stat3 and Stat5 were associated with each other (P = .017) and with a CAV1(high)/MSN(high)/IGFBP2(low) profile. All patients with tumors expressing high STAT5A/EPHA2 experienced a complete response on RT-CTX-based treatments (12/15 complete responders, P < .0001) and a longer progression-free survival (P = .024). Few tumors expressed high ANXA1/CAV1/EPHA2 and low IGFBP2, a putative dasatinib response-related profile, whereas high ANXA1 was associated with shorter overall survival (P = .003). In conclusion, Stat activation is common in LA-SCCHN, where overexpression of STAT5A and EPHA2 may predict for response to RT-CTX treatments. The STAT5A/EPHA2 profile seems of particular interest for validation in larger cohorts and in multiple tumor types because markers for the positive selection of patients to benefit from CTX-containing treatments are currently lacking.

Primary laryngeal lymphoma: report of 3 cases and review of the literature.

BACKGROUND: Extranodal lymphomas limited to the larynx are rare, accounting for less than 1% of all laryngeal neoplasms. The aim of this study was to report the experience of our department in the management of these aggressive lesions, as they require special diagnostic and therapeutic attention. METHODS: The case records of 3 patients with the diagnosis of lymphoma involving the larynx were retrospectively reviewed. RESULTS: The histopathological diagnosis revealed 1 case of marginal zone lymphoma mucosa-associated lymphoid tissue type, 1 case of T-lymphoblastic lymphoma, and 1 case of a rare coexistence of in situ squamous cell carcinoma with an isolated intravascular (angioimmunoblastic) lymphoma of peripheral T-cell origin. Details of the presentation, diagnostic procedures, treatment, and outcome of these patients were presented. CONCLUSIONS: Primary laryngeal lymphoma is a rare entity. Early symptoms are subtle and nonspecific, and confirmation of the diagnosis is often difficult. Because of the rarity of this tumor type, the optimal management remains controversial and it seems that should be managed not as a distinct disease entity but as an unusual presentation of non-Hodgkin lymphoma, according to the recent treatment trends.